We have produced severe vitamin B12 deficiency in rhesus monkeys by feeding them a defined experimental diet under controlled conditions. Five years after institution of the deficient diet, the morphology and counts of peripheral blood and bone marrow are normal. Gross visual impairment appeared in five of the monkeys between 33 and 45 months after the institution of the vitamin B12 deficient diet. Subsequently, in three of the visually impaired animals, a gradually progressive spastic paralysis of their hind limbs developed. Autopsies of seven deficient animals showed degeneration of the peripheral visual pathway in all and of white matter in the spinal cord in five. Degeneration of several cranial nerve roots was found in four monkeys and a mild diffuse degeneration of cerebral white matter in four. The lesions in all affected parts of the central nervous system were bilaterally symmetrical and were indistinguishable from those due to B12 deficiency in the human. No abnormalities were found in one B12 supplemented control animal. It is proposed to continue these studies (1) pursuing to completion the light and electron microscopic studies already begun (2) expanding these observations in 5 newly purchased animals which are now on the deficient diet in order to study the ultrastructural changes in the CNS at their earliest stage (3) examining the correlation between clinical, histological and ultrastructural abnormalities and biochemical and enzymatic alterations that have been described for vitamin B12 deficiency. BIBLIOGRAPHIC REFERENCES: Agamanolis, D.P., Victor M., Chester, E. M., Banker, B.Q., Kark, J.A., Hines, J.D. and Harris, J.W.: Neuropathologic changes in Vitamin B12 deficient monkeys. J. Neuropath Exp. Neurol. 35:104, 1976. Agamanolis, D.P., Chester, E.M., Victor, M., Kark, J.A., Hines, J.D. and Harris, J.W.: Neuropathology of Vitamin B12 deficiency in monkeys. Neurology 26: 905-914, 1976.